Document Detail


Expression regulation and function of heparan sulfate 6-O-endosulfatases in the spermatogonial stem cell niche.
MedLine Citation:
PMID:  20855470     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glial cell line-derived neurotrophic factor (GDNF) is a heparan sulfate (HS)-binding factor. GDNF is produced by somatic Sertoli cells, where it signals to maintain spermatogonial stem cells (SSCs) and reproduction. Here, we investigate the roles of extracellular HS 6-O-endosulfatases (Sulfs), Sulf1 and Sulf2, in the matrix transmission of GDNF from Sertoli cells to SSCs. Although Sulfs are not required for testis formation, Sulf deficiency leads to the accelerated depletion of SSCs, a testis phenotype similar to that of GDNF+/- mice. Mechanistically, we show that Sulfs are expressed in GDNF-producing Sertoli cells. In addition, reduced Sulf activity profoundly worsens haplo-deficient GDNF phenotypes in our genetic studies. These findings establish a critical role of Sulfs in promoting GDNF signaling and support a model in which Sulfs regulate the bioavailability of GDNF by enzymatically remodeling HS 6-O-desulfation to release GDNF from matrix sequestration. Further, Sertoli cell-specific transcriptional factor Wilm's tumor 1 (WT1) directly activates the transcription of both Sulf1 and Sulf2 genes. Together, our studies not only identify Sulfs as essential regulators of GDNF signaling in the SSC niche, but also as direct downstream targets of WT1, thus establishing a physiological role of WT1 in Sertoli cells.
Authors:
Aliete Langsdorf; Valerie Schumacher; Xiaofeng Shi; Thanh Tran; Joseph Zaia; Sanjay Jain; Mary Taglienti; Jordan A Kreidberg; Alan Fine; Xingbin Ai
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-20
Journal Detail:
Title:  Glycobiology     Volume:  21     ISSN:  1460-2423     ISO Abbreviation:  Glycobiology     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-12-28     Completed Date:  2011-06-01     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  152-61     Citation Subset:  IM    
Affiliation:
The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / physiology
Gene Expression Regulation
Glial Cell Line-Derived Neurotrophic Factor / genetics,  metabolism
Heparitin Sulfate / metabolism
Humans
Male
Mice
Nuclear Proteins / genetics,  metabolism
Promoter Regions, Genetic
Rats
Sertoli Cells / metabolism*
Signal Transduction / physiology
Spermatogonia* / metabolism
Stem Cell Niche / metabolism
Stem Cells / metabolism
Sulfatases* / genetics,  metabolism
Sulfotransferases* / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
1R01AG034939/AG/NIA NIH HHS; R01 DK082531/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Glial Cell Line-Derived Neurotrophic Factor; 0/Nuclear Proteins; 0/WTAP protein, human; 9050-30-0/Heparitin Sulfate; EC 2.8.2.-/Sulf1 protein, mouse; EC 2.8.2.-/Sulfotransferases; EC 3.1.6.-/Sulf2 protein, mouse; EC 3.1.6.-/Sulfatases
Comments/Corrections

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